Jan Seppälä

Carbon-11 acetate PET/CT based dose escalated IMRT in prostate cancer

PURPOSE To demonstrate the theoretical feasibility of [(11)C]acetate PET/CT in delineating the malignant intraprostatic lesions (IPLs) in prostate cancer and to use the data in external beam radiotherapy to boost the biologically defined target volume (BTV). METHODS AND MATERIALS Twelve men with intracapsular prostate carcinoma were imaged with [(11)C]acetate PET/CT and the data were used to delineate the BTV. Six dynamic IMRT plans were generated to each patient: a standard IMRT (sIMRT) plan with a 77.9 Gy dose to PTV (prostate gland with a 6-mm margin) and a simultaneous integrated boost IMRT (SIB(IMRT)) plan to deliver 77.9 Gy, 81 Gy, 84 Gy, 87 Gy and 90 Gy to the BTV and 72 Gy to the rest of PTV. To study the theoretical dose escalation based on the delineation of BTV, tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs) of bladder and rectum were calculated and compared between the treatment plans. RESULTS [(11)C]Acetate was used to delineate the IPLs of all 12 patients. With every patient the TCP was increased with SIB(IMRT) without increasing the NTCP of the bladder or rectum. The probability of uncomplicated control (PUC) was increased on average by 28% with the SIB(IMRT) treatment plans. The highest PUC was achieved with an average dose of 82.1 Gy to the BTV. CONCLUSIONS Our study indicates that [(11)C]acetate can be used to define the IPLs and in combination with SIB(IMRT) the defined areas can theoretically be treated to ultra high doses without increasing the treatment toxicity. These results motivate the formal validation of [(11)C]acetate PET for biological dose planning in prostate cancer.

Tangential volumetric modulated arc therapy technique for left-sided breast cancer radiotherapy

BackgroundThe aim of the present study was to introduce a new restricted tangential volumetric modulated arc therapy (tVMAT) technique for whole breast irradiation and compare its dosimetric properties to other currently used breast cancer radiotherapy techniques.MethodTen consecutive women with left-sided breast cancer were enrolled in this retrospective study. Four treatment plans were generated for each patient: 1) standard tangential field-in-field (FinF), 2) tangential intensity modulated radiotherapy (tIMRT), 3) tangential VMAT (tVMAT) with two dual arcs of 50-60° and 4) continuous VMAT (cVMAT) with a dual arc of 240°. The plans were created with Monaco® (tIMRT, tVMAT and cVMAT) and Oncentra® (FinF) treatment planning systems.ResultsWith both VMAT techniques significantly higher cardiac avoidance, dose coverage and dose homogenity were achieved when compared with FinF or tIMRT techniques (p < 0.01). VMAT techniques also decreased the high dose areas (above 20 Gy) of ipsilateral lung. There were no significant differences in the mean dose of contralateral breast between the tVMAT, tIMRT and FinF techniques. The dose coverage (V47.5 Gy) was greatest with cVMAT. However, with cVMAT the increase of contralateral breast dose was significant.ConclusionsThe present results support the hypothesis that the introduced tVMAT technique is feasible for treatment of left-sided breast cancer. With tVMAT dose to heart and ipsilateral lung can be reduced and the dose homogeneity can be improved without increasing the dose to contralateral breast or lung.

A method to improve target dose homogeneity of craniospinal irradiation using dynamic split field IMRT

PURPOSE Craniospinal irradiation (CSI) is technically very challenging and field edge matching is needed because of the mechanical limitations of standard linear accelerators. We assessed the feasibility of intensity-modulated radiotherapy (IMRT) in CSI to overcome the standard feathering and dose inhomogeneities associated with the standard feathering technique in the junction areas. MATERIALS AND METHODS The use of IMRT in CSI was studied with five patients CT scanned in the supine position. Isocentric treatment plans of three dimensional conventional radiotherapy (3D-CRT) and split field IMRT (sfIMRT) with dynamic intrafractional feathering were created with the same field setup and the resulted dose distributions were compared. The effect of treatment inaccuracy was simulated with an intentional shift of +/-3mm with both treatment plans. Dosimetric verification of the sfIMRT treatment plan was performed with radiographic films placed in a phantom. RESULTS The sfIMRT treatment plans resulted in a better dose coverage and uniformity in the target volume. The +/-3mm shift had only a minor effect on the dose distribution of the sfIMRT treatment plan whereas with the 3D-CRT the shift resulted in an error of +/-38% of the calculated dose in the spinal cord. The measured dose distribution of the sfIMRT treatment plan correlated well with the calculations. CONCLUSIONS Improved dose homogeneity in the target volume was achieved with the sfIMRT compared to the conventional 3D-CRT treatment plan. With the sfIMRT technique only a single treatment plan is required to deliver the total treatment dose and the resulting dose distribution is also less volatile for technical uncertainties of the treatment.

Prognostic value of tumour blood flow, [18F]EF5 and [18F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy

PurposeIn order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour’s biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [18F]FDG, a new hypoxia tracer [18F]EF5 and the perfusion tracer [15O]H2O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy.MethodsThe study group comprised 22 patients with confirmed squamous cell carcinoma of the head and neck who underwent a PET/CT scan using the above tracers before any treatment. Patients were later treated with a combination of radiochemotherapy and surgery. Parametric blood flow was calculated from dynamic [15O]H2O PET images using a one-tissue compartment model. [18F]FDG images were analysed by calculating standardized uptake values (SUV) and metabolically active tumour volumes (MATV). [18F]EF5 images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A T/M ratio of 1.5 was considered a significant threshold and used to determine tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were finally correlated with the pretreatment clinical findings (overall stage and TNM stage) as well as the outcome following radiochemotherapy in terms of local control and overall patient survival.ResultsTumour stage and T-classification did not show any significant differences in comparison to the patients’ metabolic and functional characteristics measured on PET. Using the Cox proportional hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR = 1.108), maximum [18F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on patient survival in the log-rank test, although [18F]EF5 maximum T/M ratio was the closest (p = 0.109). By contrast, tumour blood flow was not correlated with any of the clinical endpoints. There were no statistically significant correlations among [18F]FDG SUVmax, [18F]EF5 T/M ratio and blood flow.ConclusionOur study in a limited number of patients confirmed the importance of MATV in the prognosis of locally advanced squamous cell carcinoma of the head and neck. It is of interest that high uptake of the hypoxia tracer [18F]EF5 showed a stronger correlation with a poor clinical outcome than [18F]FDG uptake. This confirms the importance of hypoxia in treatment outcome and suggests that [18F]EF5 may act as a surrogate marker of radioresistance.

Experimental and Analytical Comparisons of Tissue Dielectric Constant (TDC) and Bioimpedance Spectroscopy (BIS) in Assessment of Early Arm Lymphedema in Breast Cancer Patients after Axillary Surgery and Radiotherapy

BACKGROUND Early diagnosis of breast cancer treatment-related lymphedema (BCRL) is of great importance for longstanding treatment results. Tissue dielectric constant (TDC) and bioimpedance spectroscopy (BIS) both have a potential for early diagnosis, but have not been compared. METHODS AND RESULTS One hundred women, treated for breast cancer with breast surgery, axillary dissection, and radiotherapy, were examined within one year after breast cancer treatment, as part of the follow-up procedure. Affected/at-risk and contralateral arms were measured with the TDC technique specific to localized skin water content and the BIS technique assessing arm extracellular fluid (ECF). Thirty-eight patients were clinically diagnosed for lymphedema (38.0%). The sensitivity and specificity for the TDC method were 65.8% and 83.9%, and for BIS method 42.1% and 93.5%, (p < 0.001 and NS), respectively. Of all lymphedema, 18.4% were detected only by TDC and 2.6% by BIS. Affected arm to contralateral arm TDC ratios for upper arm and forearm, 1.56 ± 0.49 and 1.28 ± 0.33, demonstrating the localized feature of the TDC measurements were significantly greater than the BIS arm ratio 1.12 ± 0.12 (both p < 0.001). CONCLUSIONS Discrepancies between TDC and BIS techniques in assessing lymphedema are related to different measurement techniques and assessed tissue water components. Independently of selected technique-specific threshold limit, the TDC technique was more sensitive than the BIS technique in the early assessment of BCRL and demonstrated that nearly 20% of early lymphedema are only superficially localized. The results further supported the complementary role of TDC and arm volume measurements as a highly diagnostic method for early lymphedema.

Increased beam attenuation and surface dose by different couch inserts of treatment tables used in megavoltage radiotherapy

The use of solid carbon fiber table materials in radiotherapy has become more common with the implementation of image‐guided radiotherapy (IGRT), since the solid materials give less imaging artifacts than the so‐called tennis racket couchtops. The downside of the solid carbon fiber couch inserts is that they increase the beam attenuation, resulting in increased surface doses and inaccuracies in determine the dose in the patient. The purpose of this study was to evaluate the interaction of 6 and 15 MV photons with eight different couch inserts. The presented results enable direct comparison of the attenuation properties of the studied couchtops. With a direct posterior beam the maximum attenuations reach 3.6% and 2.4% with 6 and 15 M V, respectively. The measured maximum attenuation by a couchtop with an oblique gantry angle was 10.8% and 7.4% at 6 and 15 MV energies, respectively. The skin‐sparing effect was decreased substantially with every couchtop. The highest increases in surface doses were recorded to be four‐ and threefold, as compared to the direct posterior open field surface doses of 6 and 15 MV, respectively. In conclusion, the carbon fiber tabletops decrease the skin‐sparing effect of megavoltage photon energies. The increased beam attenuation and skin doses should be taken into account in the process of treatment planning. PACS number: 07.90.+c

Open-Ended Coaxial Dielectric Probe Effective Penetration Depth Determination

We have performed a series of experiments, which demonstrate the effect of open-ended coaxial diameter on the depth of penetration. We used a two-layer configuration of a liquid and movable cylindrical piece of either Teflon or acrylic. The technique accurately demonstrates the depth in a sample for which a given probe diameter provides a reasonable measure of the bulk dielectric properties for a heterogeneous volume. In addition, we have developed a technique for determining the effective depth for a given probe diameter size. Using a set of simulations mimicking four 50- Ω coaxial cable diameters, we demonstrate that the penetration depth in both water and saline has a clear dependence on the probe diameter, but is remarkably uniform over frequency and with respect to the intervening liquid permittivity. Two different 50- Ω commercial probes were similarly tested and confirm these observations. This result has significant implications to a range of dielectric measurements, most notably in the area of tissue property studies.

A dosimetric phantom study of dose accuracy and build-up effects using IMRT and RapidArc in stereotactic irradiation of lung tumours

Background and purposeStereotactic lung radiotherapy (SLRT) has emerged as a curative treatment for medically inoperable patients with early-stage non-small cell lung cancer (NSCLC) and the use of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc treatments (VMAT) have been proposed as the best practical approaches for the delivery of SLRT. However, a large number of narrow field shapes are needed in the dose delivery of intensity-modulated techniques and the probability of underdosing the tumour periphery increases as the effective field size is decreased. The purpose of this study was to evaluate small lung tumour doses irradiated by intensity-modulated techniques to understand the risk for dose calculation errors in precision radiotherapy such as SLRT.Materials and methodsThe study was executed with two heterogeneous phantoms with targets of Ø1.5 and Ø4.0 cm. Dose distributions in the simulated tumours delivered by small sliding window apertures (SWAs), IMRT and RapidArc treatment plans were measured with radiochromic film. Calculation algorithms of pencil beam convolution (PBC) and anisotropic analytic algorithm (AAA) were used to calculate the corresponding dose distributions.ResultsPeripheral doses of the tumours were decreased as SWA decreased, which was not modelled by the calculation algorithms. The smallest SWA studied was 2 mm, which reduced the 90% isodose line width by 4.2 mm with the Ø4.0 cm tumour as compared to open field irradiation. PBC was not able to predict the dose accurately as the gamma evaluation failed to meet the criteria of ±3%/±1 mm on average in 61% of the defined volume with the smaller tumour. With AAA the corresponding value was 16%. The dosimetric inaccuracy of AAA was within ±3% with the optimized treatment plans of IMRT and RapidArc. The exception was the clinical RapidArc plan with dose overestimation of 4%.ConclusionsOverall, the peripheral doses of the simulated lung tumours were decreased by decreasing the SWA. To achieve adequate surface dose coverage to small lung tumours with a difference less than 1 mm in the isodose line radius between the open and modulated field, a larger than 6 mm SWA should be used in the dose delivery of SLRT.

Hypofractionated stereotactic body radiotherapy for localized prostate cancer – first Nordic clinical experience

Abstract Background: The use of hypofractionated stereotactic body radiotherapy (SBRT) as primary treatment modality in clinically localized prostate cancer (PCa) is emerging, because the low α/β-ratio favors the use of high dose per fraction in PCa. There is a need for more data about SBRT, especially in high-risk PCa patients. The purpose of this retrospective study was to evaluate the safety and the short-term efficacy of robotic SBRT in a clinical patient cohort with localized PCa including also high-risk patients (D’Amico risk stratification). Materials and methods: A total of 240 consecutive patients with clinically localized PCa were treated primarily with SBRT to total doses of 35 Gy or 36.25 Gy in 5 fractions using a robotic SBRT device (CyberKnife®). All risk groups (D’Amico risk stratification) were represented as follows: 48 (22%), 59 (27%) and 111 (51%) of the patients representing low-, intermediate- and high-risk group, respectively. Data on acute and intermediate-term toxicities and early PSA responses were analyzed. Results: Neither acute grade 3 or higher GU nor rectal toxicity was observed. Regardless of the fact that 29 (13.3%) patients experienced intermediate-term toxicity requiring diagnostic interventions, the rates of intermediate-term grade 3 GU, rectal and infectious toxicity were low, 1.8%, 0.9% and 1.4%, respectively. A biochemical relapse was observed in ten (4.6%) patients. With the median follow-up time of 23 months the biochemical relapse-free survival (bRFS) rate was 100%, 96.6% and 92.8% in low-, intermediate- and high-risk group, respectively. Conclusions: The toxicity of robotic SBRT in a large clinical cohort of PCa patients was tolerable and the early PSA response was good in all risk groups. The hypofractionated SBRT offers a possibility to high dose per fraction and to provide the whole radiotherapy treatment within two to three weeks.

Flattening filter free technique in breath-hold treatments of left-sided breast cancer: The effect on beam-on time and dose distributions.

BACKGROUND AND PURPOSE The use of flattening filter free (FFF) beams has potential to speed up deep-inspiration breath-hold treatments. In this study, the beam-on time and dose characteristics of left-sided breast treatment plans with FFF and flattened beams were evaluated. MATERIAL AND METHODS Twelve plans were generated for 20 patients. The techniques utilized were volumetric modulated arc therapy with two limited tangential arcs (tVMAT) and tangential intensity modulated radiotherapy with dynamic (dIMRT) as well as step-and-shoot (FinF) dose delivery. Each technique was planned with FFF and flattened beams with 6 and 10MV photons. All plans were irradiated and the beam-on times were measured. Dose characteristics of planning target volume (PTV) and organs at risk (OAR) were evaluated. RESULTS The mean beam-on times were reduced by 18-39% using FFF. Mean PTV dose coverage was least reduced with tVMAT (0.6-0.8%) compared to dIMRT (4%) and FinF (5.6-9.1%), when FFF beams were used instead of flattened beams. Only small differences were observed in OAR doses between equivalent plans (FFF vs. flattened). CONCLUSIONS A significant reduction was observed in beam-on time when utilizing FFF beams with tVMAT, dIMRT and FinF. tVMAT was the only technique for which the use of FFF did not degrade the treatment plan dose distributions.